The differential catalytic activity of alternatively spliced cdk2 alpha and cdk2 beta in the G1/S transition and early S phase.
Progression through the G1/S transition of the cell cycle is regulated by cyclin E/cdk2 and cyclin A/cdk2 complexes. We demonstrate that there are two forms of murine cdk2 (cdk2 alpha and beta). Cdk2 alpha consist of 298 amino acids, while cdk2 beta contains a 48-amino-acid insert between Met (196) and Val (197) of cdk2 alpha. Cdk2 beta results from differential splicing of the primary RNA transcript of the cdk2 gene. Although human cdk2 genomic DNA contained the sequence of the insert for the beta form, cdk2 beta was not detected by either Western blot or RT-PCR in human T-cells or several other human cell lines. Cdk2 beta expression in murine cells was similar to that of the phosphorylated, catalytically active form of cdk2 alpha. Cdk2 alpha and cdk2 beta have very similar binding activity to cyclin E and to the cdk inhibitor p27Kip1. The alternatively spliced cdk2 beta possesses catalytic activity in vivo and in vitro. The differential catalytic activity of these two forms of cdk2 suggests that cdk2 alpha and cdk2 beta may perform different functions at or near the G1/S transition and early S phase.
Kwon
T K
TK
Laboratory of Immunology, National Institute on Aging, NIH, Baltimore, Maryland 21224-2780, USA.
Buchholz
M A
MA
Jun
D Y
DY
Kim
Y H
YH
Nordin
A A
AA
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases; D002384:Catalysis; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005091:Exons; D016193:G1 Phase; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016196:S Phase; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000201:enzymology*; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases